to interrupt transmission of nerve impulses at the neuromuscular juntion

depolarizing NMB mimic the action of

Ach

non-depolarizing NMB interfere with action of

Ach

how are pharmacodynamics of NMB determined

by measuring speed of onset and duration of NM blockade

what is a common method for determining the type, speed of onset, magnitude, and duration of NM blockade

to observe or record the skeletal muscle response that is evoked by a supramaximal electrical stimulus that is delivered from a peripheral nerve stimulator

contraction of what muscle using 1 hz of electrical stimulation to the ulnar nerve is used to assess the effect of NMB drugs

adductor pollicis muscle (muscle in hand that controls movement of the thumb)

-a single twitch using 1 hz from a peripheral nerve stimulator.

ED95

the dose needed to produce 95% suppression of the single twitch response (1 Hz)

-this is how potency and effect is measured between all NMB drugs

ED95 represents potency of MNBD in the presence of what

nitrous oxide-barbiturate-opioid anesthesia.

-this is always assumed unless stated otherwise

in the presence of volatile anesthetics the ED95 is greatly _______?

decreased

-decreased plasma concentrations of NMBDs is required to produce a given degree of blockade in the presence of VA

What muscles are affected first with NMBD

small rapid moving skeletal muscles (eyes and digits) before those of the abdomen (diaphragm)

the onset of neuromuscular blockade after giving a non-depolarizing NMBD is more rapid but less intense at the _______ muscles than the _______ muscles.

laryngeal muscles than the peripheral muscles (adductor pollicis)

-the reason for this is because fast muscle fibers are present in muscle used to close the glottis whereas slow fibers are in the adductor pollicis. The density of Ach receptors is greater in the fast fibers so more receptors need to be occupied to block a fast muscle than a slow muscle

The dose of NMBD necessary to produce a given degree of neuromuscular blockade at the diaphragm is about _____ the required to produce similar blockade of the adductor pollicis muscle.

twice

-adductor pollicis monitoring is a poor indicator of laryngeal relaxation, whereas facial nerve stimulation and monitoring the response of the orbicularis oculi muscle more closely reflects the onset of neuromuscular blockade at the diaphragm

what is the best muscle to monitor the onset of NMB at the diaphragm

orbicularis oculi -muscle of the eye via stimulation of the facial nerve- ideal muscle to monitor for blockade of the larynx

2 is inhibitory by getting rid of extracellular calcium (should be similar to presynaptic)

a single twitch response evoked by using a peripheral nerve stimulator reflects events at the ________ membrane, whereas continuous stimulation of TOF reflects events at the ______ membrane

postjunctional membrane

presynaptic membrane

NMBD are highly _____ _____ soluble compounds at physiological pH

ionized water

-possess limited lipid solubility and because of this Vd is limited and is similar to ECF volume

NMB can not cross lipid membrane barriers like what?

BBB, renal tubular epithelium, GI epithelium, or placenta so they do not produce CNS effects or affect the fetus/

what are clearance, Vd, and elimination half times influenced by with NMB

age, VA's, and presence of hepatic and renal disease.

the rate of disappearance of long acting NMB from plasma is characterized by a ______ initial decline (distribution to tissues) followed by a _____ decline (clearance)

rapid

slower

potency of NMBD

ED necessary to depress single twitch depression 95% (ED95)

onset of NMBD

time from injection to onset of maximal singe twitch depression

duration of action of NMBD

time of injection to return of singe twitch height to 25% or 95%

recovery index of NMBD

time from 25% return of single twitch height to 75% return of single twitch height

clinical duration of NMBD

time from injection to recovery of the TOF ratio to >/= 0.7 or >/= 0.9

how much of non depolarizing muscle relaxant is often recommended to facilitate tracheal intubation

2 x ED95

how much suppression of single twitch response is considered evidence of adequate drug induced skeletal muscle relaxation

90% supression

Laryngospasms can be treated with small doses of what

SCh as small as 1mg/kg

A TOF ratio of ______ is considered to reflect adequate return of skeletal muscle strength to permit spontaneous ventilation after either spontaneous recovery or pharmacologic antagonism of the effects of non depolarizing NM blockade

>0.7

evidence that pharyngeal dysfunction and greater risk of aspiration is present with TOF ratio is <0.9

clinical indicators or residual NM blockade include

grip strength

ability to sustain head lift

vital capacity measurement

generation of negative inspiratory pressure

what is sequence of onset of NM blockade

small muscle (eyes and digits) are affected before trunk and abdomen and finally the intercostals and the diaphragm

-recovery occurs in reverse order, so diaphragm is first to regain normal function

What is something important to remember about NMB and CNS

conscious and sensorium remain undisturbed even in the presence of complete neuromuscular blockade ( so patient can still think and hear), patient can also still feel pain

-therefore these meds can not be substituted for anesthetic drugs.

2 alpha subunits on post synaptic cholinergic recptors

this where Ach binds and causes channel to open causing depolarization. It takes binding of both alpha subunits to open, if only one is bound thechannel remains closed

-this is also sites for NMBD

nondepolarizing bind to one or both (lack agonist activity) cause no change, receptor channel remains closed.

****if enough channels remain closed their is a blockade of neuromuscular transmission

release of hundreds of Ach that bind to alpha subunits of nAChRs (nicotinic acetylcholine receptors) on post synaptic membrane causing a change in membrane permeability to ions decreasing the transmembrane potential. this is when action potential spreads causing skeletal muscles to contract.

Release of Ach is dependent on what

Calcium levels and is triggered by the concentration of free calcium ions in the nerve terminal .